Temperature sensing analyte sensors, systems, and methods of manufacturing and using same

ABSTRACT

In some aspects, an analyte sensor is provided for detecting an analyte concentration level in a bio-fluid sample. The analyte sensor has a base, a first electrode and a second electrode wherein a thermocouple portion is provided integral with the second electrode thereby enabling on-sensor temperature measurement capability. In some embodiments, two and only two electrical contact engagement portions are provided thereby simplifying electrical contact. Manufacturing methods and systems utilizing the analyte sensors are provided, as are numerous other aspects.

RELATED APPLICATIONS

The present application is a continuation of U.S. Non-Provisionalapplication Ser. No. 13/884,694 filed Jul. 15, 2013, now U.S. Pat. No.9,188,556, and entitled “TEMPERATURE SENSING ANALYTE SENSORS, SYSTEMS,AND METHODS OF MANUFACTURING AND USING SAME” which is a 371 ofInternational Application No. PCT/US2011/059569 filed Nov. 7, 2011,entitled “TEMPERATURE SENSING ANALYTE SENSORS, SYSTEMS, AND METHODS OFMANUFACTURING AND USING SAME”, which claims priority to U.S. ProvisionalPatent Application No. 61/413,365 filed Nov. 12, 2010, entitled“TEMPERATURE SENSING ANALYTE SENSORS, SYSTEMS, AND METHODS OFMANUFACTURING AND USING SAME”, all of which are hereby incorporated byreference herein in their entirety for all purposes.

FIELD OF THE INVENTION

The present invention relates to analyte sensors that may be used todetect an analyte concentration level in a bio-fluid sample, systemsincluding the analyte sensors, and methods of using and manufacturingthe analyte sensors.

BACKGROUND OF THE INVENTION

The monitoring of analyte concentration levels in a bio-fluid may be animportant part of health diagnostics. For example, an electrochemicalanalyte sensor may be employed for monitoring of a patient's bloodglucose level as part of diabetes treatment and care. An electrochemicalanalyte sensor may be employed, for instance, for detecting an analyteconcentration level in a bio-fluid sample such as from a single sampleof blood or other interstitial fluid. For example, the bio-fluid may beobtained from the patient using a lancet (e.g., by a pinprick orneedle). Typically, after a bio-fluid sample has been obtained, thesample may then be transferred to a medium (e.g., to an analyte sensor)for measurement of the bio-fluid sample's analyte concentration level(e.g., a glucose analyte level).

It is established that such measurements may be somewhat affected bytemperature, as the reagent and the electrochemical reaction may betemperature sensitive. Prior systems have included temperature sensinginside of an analyte testing meter (e.g., a temperature sensor inside ofa blood glucose meter (BGM)). However, for various reasons, sensing oftemperature inside of the meter, albeit achieving enhanced accuracy ascompared to non-temperature compensated analyte meter systems, mayinduce some error when actual temperature on the sensor (at or near thereagent) is not properly compensated for. Accordingly, it may bebeneficial to provide an analyte sensor adapted for bio-fluid analytetesting that may more closely or more elegantly account for temperaturechanges due to the actual temperature on the analyte sensor.

SUMMARY OF THE INVENTION

In a first aspect, the present invention provides an analyte sensor. Theanalyte sensor includes a first electrode having a contact engagementportion and a sensing portion; a second electrode having a contactengagement portion and a sensing portion; an active region provided incontact with, and extending between, the sensing portions of the firstelectrode and the second electrode; and a thermocouple portioncomprising at least part of a conducting path from the active region tothe contact engagement portion of the second electrode.

In yet another aspect, the present invention provides an analyte sensor.The analyte includes a base; a first conductor made of a firstconductive material extending along the base, the first conductor havinga first contact engagement portion and a first sensing portion; a secondconductor extending along the base having a second contact engagementportion and a second sensing portion; an active region provided incontact with and extending between the first sensing portion and thesecond sensing portion; and a thermocouple portion connected between thesecond contact engagement portion and a second sensing portion of thesecond electrode, wherein the first contact engagement portion andsecond contact engagement are the only two contact engagement portionsof the analyte sensor.

In another aspect, the present invention provides an analyte testingsystem. The analyte testing system includes an analyte sensor includinga working electrode having a contact engagement portion and a sensingportion, a counter or reference electrode having a contact engagementportion and a sensing portion, an active region provided in contact withand extending between the sensing portions of working electrode and thecounter or reference electrode, and a thermocouple portion connectedbetween the contact engagement portion and a sensing portion of thecounter or reference electrode and comprising at least part of aconducting path of the counter or reference electrode; and a temperaturemeasurement circuit provided in electrical contact with the contactengagement portions.

In a method aspect, the present invention provides a method of testingan analyte sensor. The method includes providing an analyte sensor;coupling the analyte sensor to an analyte testing meter; measuring atemperature on the analyte sensor; burning a fuse member on the analytesensor; and measuring an analyte value on the analyte testing meter.

In another method aspect, the present invention provides a method ofmanufacturing an analyte sensor. The method includes the steps ofproviding a base; forming a first electrode including a first materialon the base; forming a second electrode on the base, the secondelectrode including a thermocouple portion of a second materialdifferent than the first material; applying an active region in contactwith the first electrode and the second electrode, wherein thethermocouple portion is at least part of a conducting path from theactive region.

Other features and aspects of the present invention will become morefully apparent from the following detailed description, the appendedclaims, and the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a top plan view of an example embodiment of analyte sensorincluding a temperature sensing element provided according to a firstaspect of the present invention.

FIG. 1B is a cross-sectioned side view of the example embodiment ofanalyte sensor of FIG. 1A taken along section line “1B-1B.”

FIG. 2A is an example embodiment of an analyte testing system includingon-body temperature measurement provided according to another aspect ofthe present invention.

FIG. 2B is an example embodiment of an analyte testing system includinga detailed view of the temperature measurement circuit providedaccording to another aspect of the present invention.

FIG. 3A is a top plan view of another example embodiment of an analytesensor including a fuse member and on-body temperature sensor accordingto another aspect of the present invention.

FIG. 3B is a cross-sectioned side view of the example embodiment ofanalyte sensor of FIG. 3A taken along section line “3B-3B.”

FIGS. 3C-3E are example embodiments of fuse members including reducedarea fuse regions according to aspects of the present invention.

FIG. 4 is an example embodiment of an analyte testing system includingon-body temperature sensing and fuse burning capability according toanother aspect of the present invention.

FIG. 5 is a detailed circuit diagram of an electrical circuit includinga fuse member burning circuit adapted to burn a fuse member of anembodiment of analyte sensor according to another aspect of the presentinvention.

FIG. 6 is a top plan view of another example embodiment of an analytesensor including an on-body temperature sensor and fuse member accordingto an aspect of the present invention.

FIG. 7 is a top plan view another example embodiment of an analytesensor including on-body temperature sensor according to an aspect ofthe present invention.

FIG. 8 is yet another example embodiment of an analyte sensor includingan on-body temperature sensor and fuse member according to an aspect ofthe present invention.

FIG. 9 is a flowchart illustrating methods of using the analyte sensoraccording to embodiments of the present invention.

FIG. 10 is a flowchart illustrating methods of manufacturing the analytesensor according to embodiments of the present invention.

DETAILED DESCRIPTION

According to some aspects of the present invention, an improvedtemperature-sensing analyte sensor is provided. As discussed above,although monitoring temperature inside the BGM may offer enhancedaccuracy, it is desirable to sense the temperature at a location that isrelatively closer to the actual site of the reaction, i.e., on the bodyof the analyte sensor (e.g., on the test strip). Including a temperaturesensor on the body of the analyte sensor is referred to herein as havingan “on-body temperature sensor.”

For example, in analyte testing systems that are adapted to receive ananalyte sensor in a port of an analyte testing meter, the part of theanalyte sensor that actually contains the reagent may be located at aposition outside of the physical confines of the analyte testing meter,and, therefore, may be exposed directly to the ambient environment.Because the thermal mass of the analyte sensor is substantially lowerthan of the analyte testing meter, the analyte sensor is prone to rapidchanges in temperature and may equilibrate with ambient temperature veryquickly. However, because the thermal mass of the analyte testing meteris relatively higher than the analyte sensor, the meter may more slowlyequilibrate with ambient temperature. Accordingly, the temperature ofthe actual site where the reaction is taking place may be somewhatdifferent than the temperature inside of the analyte testing meter. Thepresent invention accounts for this difference.

In the way of a real-world example, a user may take the analyte testingmeter (e.g., BGM) out of their pocket, and then may insert an analytesensor into a port of the meter. The actual site where the reagent islocated on the analyte sensor may be exposed to relatively cold weather(e.g., 30 degrees F. or less) and because of its relatively low thermalmass may quickly equilibrate so as to be at or very near to the ambienttemperature whereas the temperature inside of the analyte testing metermay be relatively warmer.

In view of this concern, the present invention provides an analytesensor having an on-body temperature sensor (e.g., that is resident onthe body of the analyte sensor) such that the actual temperature of thereagent may be approximately accounted for. The analyte sensor mayinclude first and second electrodes each having a contact engagementportion and a sensing portion, an active region provided in contactwith, and extending between, the sensing portions of the first electrodeand second electrode, and a thermocouple portion connected between thecontact engagement portion and a sensing portion of the secondelectrode. The thermocouple portion may comprise at least a part of aconducting path from the active region to the contact engagement portionof the second electrode.

More simply, a thermocouple is embodied by the first and secondelectrodes thereby forming an on-body sensor. Accordingly, in someembodiments, the analyte sensor may include two, and only two,electrical contacts thereby significantly simplifying the act of makingof an electrical connection with the analyte testing meter. The analytesensor of the present invention may be used to measure any number ofanalytes, such as glucose, fructose, lactate, keytone, microalbumin,bilirubin, total cholesterol, uric acid, lipids, triglyceride, highdensity lipoprotein (HDL), low density lipoprotein (LDL), hemoglobinA1c, etc. The analytes may be detected in, for example, whole blood,blood serum, blood plasma, interstitial fluid, urine, etc. Other typesof analytes may be measured provided a suitable reagent exists.

In other embodiments, an analyte testing system is provided. The analytetesting system includes an analyte sensor including a working electrodehaving a contact engagement portion and a sensing portion, a counter (orreference) electrode having a contact engagement portion and a sensingportion, an active region provided in contact with and extending betweenthe sensing portions of working electrode and the counter (or reference)electrode, and a thermocouple portion connected between the contactengagement portion and a sensing portion of the counter (or reference)electrode and comprising at least a part of a conducting path of thecounter electrode, and a temperature measurement circuit provided inelectrical contact with the contact engagement portions (that may numbertwo, and only two).

These and other embodiments of analyte sensors, analyte testing systemsand apparatus including the analyte sensors, and methods of using andmanufacturing the analyte sensor are described below with reference toFIGS. 1A-10.

FIGS. 1A-1B illustrate a top and a cross-sectioned side view,respectively, of a first example embodiment of an analyte sensor 100provided according to a first aspect of the present invention. Theanalyte sensor 100 may include a sensor body including a base 102preferably formed of an insulating material. The base 102 may have afirst end 104 and a second end 106 opposite the first end 104 and spacedtherefrom, and may be relatively planar in shape. The base 102 may beany suitable shape, such a rectangular, or other polygonal shapes. Othershapes may be used. The base 102 may be manufactured from of a suitablepolymer material, such as a polycarbonate, polyethylene terephthalate(PET), polyethylene naphthalate (PEN), polyimide, high densitypolyethylene, or polystyrene material, or combinations, for example.Other materials may be used. The base 102 may be manufactured by beingstamped out of a sheet of material, thermally formed, extruded, ormolded, for example.

The analyte sensor 100 includes a first electrode 108 (e.g., a workingelectrode) that in the depicted embodiment may extend along the base 102from the first end 104 to the second end 106. The first electrode 108includes a contact engagement portion 110 and a sensing portion 112. Thecontact engagement portion 110 may be enlarged relative to the extendingportion of the electrode 108, located on the first end 104, and adaptedto be contacted by an electrical contact of an analyte testing meter. Asensing portion 112 may be located on the second end 106.

Likewise, a second electrode 114 (e.g., a reference or counterelectrode) may extend along the base 102 from the first end 104 to thesecond end 106. The second electrode 114 includes a contact engagementportion 116 and a sensing portion 118. The contact engagement portion116 may be enlarged relative to an extending portion of the electrode,may be located on the first end 104, and may be adapted to be contactedby an electrical contact of an analyte testing meter. The contactengagement portions 110 and 116 may be made of the same material andhave the same approximate shape and size. Like the sensing portion 112,the sensing portion 118 may be located on the second end 106. Thesensing portion 118 may be positioned opposite of the sensing portion112.

An active region 120, that may be located at on the second end 106, isprovided in engaging contact with the first and second electrodes 108,114. The active region 120 extends between the opposed sensing portions112, 118. The active region 120 may be an electrochemically-activeregion including one or more catalytic agents or reagents adapted toreact with a biological fluid that is provided in contact with theactive region 120 during analyte measurement.

The first electrode 108 may be positioned partially underneath of theactive region 120 such that there is an electrical coupling with thefirst electrode 108. The first contact engagement portion 110 is adaptedto be in electrical contact with a first electrical contact of ananalyte testing meter 202 (See FIGS. 2A-2B). The first electrode 108 andsecond electrodes 114 may be made from any suitableelectrically-conductive material. Suitable conductive materials includecarbon, graphite, noble metals such as gold, palladium, or platinum,silver, combinations of the aforementioned, or the like. In someembodiments, the electrodes may be made from a carbon/graphite PTF,silver/silver chloride, or an electrically-conductive ink such as acarbon- and silver-containing ink. As will be described more thoroughlybelow, the electrodes 108, 114 shall include sufficiently dissimilarmaterials to produce an on-body thermocouple sensor including a suitableelectrical output according to an aspect of the invention.

Sensing portions 112, 118 of the electrodes 108, 114 may be formed on asurface of the base 102 and may include any suitable construction. Forexample, a single gap may be provided, or interleaved electrode fingersmay form multiple gaps. The active region 120, as before described, maybe applied over the sensing portions 112, 118. A suitable mask may beused for precise control and application of an applied area of theactive region 120.

The active region 120 may be adapted to promote an electrochemicalreaction between an analyte in the biological fluid sample and thecatalytic agents or reagents included in the active region 120, orotherwise generate a detectible electrical current upon being exposed tothe biological fluid sample. The mobile electrons produced may beconducted to an analyte testing meter 202 (FIGS. 2A-2B), for example. Avoltage bias is generally applied to the electrodes 108, 114 of theanalyte sensor 100 during the analyte measurement step of the testingsequence, i.e. when actually taking/recording a raw analyteconcentration measurement.

One group of catalytic agents useful for providing the active region 120may be the class of oxidase enzymes which includes, for example, glucoseoxidase (which converts glucose), lactate oxidase (which convertslactate), and D-aspartate oxidase (which converts D-aspartate andD-glutamate). In embodiments in which glucose is the analyte ofinterest, glucose dehydrogenase (GDH) may optionally be used.Pyroloquinoline quinine (PQQ) or flavin adenine dinucleotide (FAD)dependent may also be used. A more detailed list of oxidase enzymes thatmay be employed in the present invention is provided in U.S. Pat. No.4,721,677, entitled “Implantable Gas-containing Biosensor and Method forMeasuring an Analyte such as Glucose” to Clark Jr. which is herebyincorporated by reference herein in its entirety. Catalytic enzymesother than oxidase enzymes may also be used.

The active region 120 may include one or more layers (not explicitlyshown) in which the catalytic agents (e.g., enzymes) and/or otherreagents may be immobilized or deposited. The one or more layers maycomprise various polymers, for example, including silicone-based ororganic polymers such as polyvinylpyrrolidone, polyvinylalcohol,polyethylene oxide, cellulosic polymers such as hydroxyethylcellulose orcarboxymethyl cellulose, polyethylenes, polyurethanes, polypropylenes,polyterafluoroethylenes, block co-polymers, sol-gels, etc. A number ofdifferent techniques may be used to immobilize the enzymes in the one ormore layers in the active region 120 including, but not limited to,coupling the enzymes to the lattice of a polymer matrix such as a solgel, cross-linking the agents to a suitable matrix such asglutaraldehyde, electropolymerization, and formation of an array betweenthe enzymes via covalent binding, or the like.

In some embodiments, a mediator may be included within the active region120 to promote the conversion of the analyte to detectable reactionproducts. Mediators comprise substances that act as intermediariesbetween the catalytic agent and the electrode. For example, a mediatormay promote electron transfer between the reaction center wherecatalytic breakdown of an analyte takes place and the electrode.Suitable mediators may include one or more of the following: metalcomplexes including ferrocene and its derivatives, ferrocyanide,phenothiazine derivatives, osmium complexes, quinines, phthalocyanines,organic dyes as well as other substances. In some embodiments, themediators may be cross-linked along with catalytic agents directly tothe first and second electrodes 108, 114.

In some embodiments, a lid 111 may be provided overtop of the base 102.The lid 111 may be fused or otherwise adhered to the base 102 byapplication of heat and pressure, for example. Other means of fasteningthe lid 111 may be employed, such as by the use of an adhesive or asealant. The lid 111 may be formed, such as by stamping, cold forming,or heat forming. The lid 111 and base 102 when fastened togethercooperate to form a cavity 122 that may extend from the second end 106towards the location of the active region 120. The cavity 122 mayprovide a capillary channel into which a biological fluid sample appliedat the end of the cavity 122 by a user may pass. The lid 111 may bemanufactured from a deformable polymer material, such as polycarbonate,an embossable grade of polyethylenetherephthalate, or a glycol modifiedpolyethylenetherephthalate, for example. Other types of materials may beused. A polyurethane dielectric material may be applied over an areaencompassed by the lid 111 and may aid in sealing the lid 111 to thebase 102. Further details of the structure of the lid 111 and base 102,as well as attachment details may be found in U.S. Pat. No. 5,759,364.

A vent 124 in the form of a hole or perforation may be provided at anend of the cavity 122 to improve capillary action and flow of thebiological fluid sample into the cavity 122 from the second end 106 whenapplied thereat by the user. The cavity 122 may be at least partiallyformed and defined, for example, by the inner surfaces of the lid 111,base 102, and the upper surface of the active region 120. The cavity 122may have any shape, but preferably a shape that promotes capillaryaction to cause a droplet of biological fluid to be drawn into thecavity 122 when applied to the entrance of the cavity 122 by the user.The bio-fluid sample may be drawn into the cavity 122 and come intointimate contact with the active region 120. The cavity 122 may have alength of about 2 mm to 5 mm, a width of about 0.5 mm to 1.5 mm, and aheight of about 0.05 mm to 0.25 mm, for example. Other dimensions may beused.

In the depicted embodiment, the sensing portion 118 of the secondelectrode 114 includes a configuration making electrical contact withthe active region 120. For example, the active region 120 may beprovided/applied overtop of an end portion of the sensing portion 118located opposite the sensing portion 112. The second electrode 114 mayinclude a contact engaging portion 116 on the first end 104 that isadapted to make electrical contact with an electrical contact of ananalyte testing meter (e.g. analyte testing meter 202 shown in FIGS.2A-2B). In between the first end 104 and the second end 106 andextending between the sensing end 118 and the contact engaging portion116 of the second electrode 114 is a thermocouple portion 126. In thedepicted embodiment, the thermocouple portion 126 is connected between acold sensing junction 126A on the sensing portion 118 and a hot sensingjunction 126B on the contact engagement portion 116. The other portionof the thermocouple comprises a portion of the first electrode 108.

To establish a thermocouple, the thermocouple portion 126 may bemanufactured from a material that is different than (dissimilar) to thematerial used to manufacture the first electrode 108. In the depictedembodiment, the thermocouple portion 126 comprises a part of theconducting path 128 (shown in phantom lines). The conducting path 128during administration of a temperature test is the same as for ananalyte measurement test. A voltage bias is applied across the contactengagement portions 110, 116 and a current is caused to flow through thefirst electrode 108, active region 120, and second electrode 114. Inparticular, the thermocouple portion 126 is part of the conducting pathbetween the active region 120 and the contact engagement portion 116 ofthe second electrode 114. In other words, during the testing/measurementstep of the testing sequence wherein a voltage bias is applied acrossthe contact engagement portions 110, 116 and an analytereading/measurement is obtained, the current for thatreading/measurement passes through the thermocouple portion 126. Thus,it should be recognized that the thermocouple portion 126 lies in adirect current conducting path 128 during both the temperaturemeasurement phase and the analyte measurement phase of the testingsequence. Generally, the temperature measurement phase takes placefirst, followed by the analyte measurement phase.

In the illustrated embodiment of FIGS. 1A-1B, the thermocouple portion126 is a trace of a carbon-based material, such as a carbon-containingink. In particular, in the depicted embodiment, the contact engagementportion 116 and the sensing portion 118 may be manufactured from thesame material as the first electrode 108 (e.g., a gold film). Thethermocouple portion 126 may then be applied overtop of the contactengagement portion 116 and the sensing portion 114 at the junctions126A, 126B as a carbon-based trace.

In particular, the thermocouple portion 126 must comprise a differentconductive material than a portion of the first electrode 108. In thedepicted embodiment, the first electrode 108 may be a noble metal (e.g.,a gold, platinum, or palladium film) and the thermocouple portion 126may be a trace of a carbon-based material. However, any two sufficientlydissimilar materials may be used that provided a sufficient thermocoupleeffect.

By forming a thermocouple including the first electrode 108 and thethermocouple portion 126, a representative temperature measurement maybe obtained by a temperature measurement circuit 204 (FIGS. 2A-2B) ofthe analyte testing meter 202 being electrically coupled thereto. Thetemperature measurement may be based upon thermoelectric principles(e.g., the Peltier-Seebeck effect). Once a temperature value has beenobtained in the temperature measurement phase, that temperature valuemay be used to provide a temperature correction constant (C_(T)) toappropriately adjust the analyte measurement taken on the analyte sensor100 for temperature on the analyte sensor 100 at or near the location ofthe active region 120. Accordingly, the actual ambient temperature onthe analyte sensor 100 at a location near the site of the active region120 may be approximately accounted for. This temperature correction maybe in addition to a calculation adjustment that is made to accommodatefor lot-to-lot or batch-to-batch variations wherein a calibrationconstant (C_(C)) is determined and used in the calculation of theanalyte concentration.

In the depicted embodiment, the analyte sensor 100 may include two, andonly two, contact engagement portions 110, 116. In other words, thecontact engagement portions 110, 116 may be the only contact engagementportions on the analyte sensor 100. As mentioned above, thisdramatically simplifies the making of an electrical contact with theanalyte sensor 100, by requiring only two electrical contacts 206A, 206Bin the analyte testing meter 202 that are adapted to engage the contactengagement portions 110, 116.

In some embodiments, the thermocouple portion 126 may be printed ontothe base 102 and overtop of parts of the contact engagement portion 116and the sensing portion 118 with a conductive ink by a screen printingprocess, ink jet process, or other deposition process, for example. Thethermocouple portion 126 may have a width (Wt) of about 0.5 mm to about1.5 mm, a length (Lt) of about 5 mm to about 25 mm, and a thickness ofabout 0.01 mm to about 0.1 mm, for example. Other sizes may be used. Ina preferred embodiment, a conductive ink may be used, such as acarbon-based ink. However, any suitable conductive electrode ink may beused.

As shown in FIG. 1A, the analyte sensor 100 may include a length (L) ofbetween about 15 mm and 35 mm, for example. The analyte sensor 100 mayinclude a maximum width (W) of between about 3 mm and 10 mm, forexample. Other length (L) and width (W) dimensions may be used.

In operation, upon insertion of a droplet of biological fluid sampleinto the cavity 122 such that the fluid comes into contact with theactive region 120, and upon application of a suitable voltage biasacross the electrodes 108, 114 (e.g., about 300 mV), an electricalcurrent may be generated that may be proportional to a concentration ofthe analyte present in the biological fluid sample. This sensedelectrical current may then be conducted by the electrical circuitincluding the first and second electrodes 108, 114, the thermocoupleportion 126, the electrical contacts 206 a, 206 b, and an analytemeasurement circuit 208 (See FIG. 2). The calculation of the analytemeasurement may be by any currently known method. As discussed above,reagent variations are generally accounted for by using a calibrationconstant (C_(C)). However, either the calibration constant (C_(C)) orthe analyte concentration calculation, according to an aspect of theinvention, may be adjusted with a temperature compensation constant(C_(T)) that is obtained by the temperature measurement circuit 204 aswill be described more fully below. The measured analyte concentration(appropriately compensated for analyte variations and temperature) maythen be displayed in any suitable readout form, such as in a digitaldisplay of the analyte testing system 200 (e.g., a blood glucose meter)as shown in FIGS. 2A-2B.

In more detail, FIGS. 2A-2B illustrate a analyte testing system 200including an analyte testing meter 202 and an analyte sensor 100 of thetype described in FIGS. 1A-1B electrically coupled thereto. Inaccordance with an aspect of the invention, the analyte testing meter202 includes conventional components such as processor 205, memory 210,display 215 (e.g., a liquid-crystal display or the like), user interface220 (e.g., push buttons, keys, a scroll wheel or ball, touch screens, orany combination thereof), power source 222 (e.g., a 3.0 V power source),power management 223, device interface 224, and electrical contacts206A, 206B. The processor 205 may be any suitable processor. Forexample, the processor 205 may be any microprocessor device orcollection of microprocessor devices that are capable of receiving thesignals and executing any number of program routines, and may be amicrocontroller, microprocessor, digital signal processor, or the like.For example, a suitable processor is a SoC microprocessor (e.g., aCortex M3 equipped microprocessor) available from ST Microelectronics orEnergy Micro. Data received and/or processed by the processor 205 may bestored in memory 210, which may store software routines that may beadapted to process raw analyte data and determine analyte measurementvalues, and carryout a temperature measurement sequence.

In operation, as an analyte sensor 100 including an on-board temperaturesensor is inserted into a port of the analyte testing meter 202 andcontact is made between the electrical contacts 206A, 206B and thecontact engagement portions 110, 116 (thereby making contact with eachelectrodes 108, 114), the microprocessor 205 (e.g., a System On Chip(SOC)) may be awakened. This may be provided by a conventionalresistance measuring circuit in the analyte measurement circuit 208, orby simply powering up the analyte testing meter 202, for example. Aroutine in software then causes a switch 209 to engage the temperaturemeasurement circuit 204 to enable execution of a temperature measurementsequence. The switch 209 may be any suitable switch, such as amultiplexor.

The temperature measurement circuit 204, as best shown in FIGS. 2A and2B, functions to record a changing voltage (Vout) that is proportionalto a ΔT across the analyte sensor 100. In particular, the changingvoltage (Vout) may be caused by a change in the temperature between thecold junction 126A and hot junction 126B of the analyte sensor 100 dueto exposure to ambient temperature. The switch 209 may be activated by asuitable signal from processor 205 to cause an electrical connectionbetween the temperature measurement circuit 204 and the analyte sensor100. Once connected, the temperature measurement circuit 204 may executea temperature sensing routine of the analyte testing sequence. Oncestarted, a voltage differential may be provided to a differentialamplifier 240 and an output may be provided that is proportional to theaforementioned ΔT. A Vout signal from the amplifier 240 may beamplified, if needed, by optional amplifier 242 and converted by A/Dconverter 244 to provide a digital output signal in line 246 to theprocessor 205 that is indicative of a ΔT between the cold and hotjunctions 126A, 126B of the analyte sensor 100.

Likewise, the temperature sensing routine may cause an absolutetemperature sensor 225 located in the port of the analyte testing meter202 and proximate to the cold junction 126A to measure an absolutetemperature as another voltage output. The absolute temperature digitalsignal received by the processor 205 in line 245 that is indicative ofthe temperature at the cold junction 126A and the voltage output digitalsignal representative of ΔT in line 246 may be summed by the temperaturesensing routine operating in the processor 205 and may be stored inmemory 210.

From these digital output values the temperature correction constant(C_(T)) may be obtained either directly or through the use of a look uptable or via calculation using a mathematical function. This temperaturecorrection constant C_(T) may be used along with a calibration constantC_(C) that is either manually input by the user, read from the packaging(e.g., in the case of multi-sensor packages), or otherwise obtained byinterfacing with various electrical contact traces on the analyte sensor100 (not shown).

FIGS. 3A-3B illustrate an example alternative embodiment of an analytesensor 300 according to another aspect of the invention. The structureof the analyte sensor 300 is similar to the aforementioned FIGS. 1A-1Bembodiment. In particular, the analyte sensor 300 includes a firstelectrode 308 having a contact engagement portion 310 and a sensingportion 312, a second electrode 314 having a contact engagement portion316 and sensing portion 318, an active region 320 coupled to theelectrodes 308, 314 at the sensing portions 312, 318, and a thermocoupleportion 326 as above-described. However, in this embodiment, the analytesensor 300 further includes a fuse member 328. The fuse member 328 mayextend between, and electrically connect, the first electrode 308 andthe second electrode 314. The fuse member 328 may be at least partiallysurrounded by a void 331. The void 331 may function to allow any gasesfrom the burning of fuse member 328 a place to expand into.

In more detail, the fuse member 328 may be formed of any suitablematerial that may be burnt (e.g., blown) by the application of apredefined voltage and/or current from a fuse member burning circuit 410in an analyte testing meter 402 as shown in FIGS. 4-5. In the depictedembodiment, the fuse member 328 may be manufactured from the samematerials as the first conductor 308 (e.g., a gold film). However,alternatively, the fuse member 328 may be manufactured from any suitablefusing material, and may be a different material than either the firstor second electrodes 308, 314. In some embodiments, the fuse member 328may include a fuse region of reduced area to control a burn location ofthe fuse member 328. The fuse region of reduced area may be formed by anotch or simply by reducing the thickness or other dimension of the fusematerial in the fuse region as compared to other areas of the fusemember 328. Since the fuse member 328 is burned by utilizing the contactengagement portions 310, 316, the fuse member 328 should be configuredto exhibit a burn value that is less than a voltage bias that will beapplied to the analyte sensor 300, i.e., across the active region 320during the analyte measurement phase of the analyte testing sequence.The burn value (Vb) is defined herein as a value of voltage or currentthat causes the fuse member 328 to burn fully (fail) thereby eliminatingan electrical path across the fuse member 328, i.e., effectively burning(or blowing) the fuse member 328. Generally, the applied bias voltageacross the analyte sensor 300 during an analyte measurement sequence isof the order of about 275 mV to about 625 mV. Therefore, in someembodiments, the burn value (Vb) for the fuse member 328 should be about250 mV or less. In this way, the fuse member 328 may be included in away that does not require additional electrical contacts on the analytesensor 300. As shown, the fuse member 328 may be sandwiched between thebase 302 and the lid 311. A sealant 332 may be used to secure the lid311 to the base 302 should cause the fuse member 328 be sealed relativeto the cavity 322. Optionally, the lid 311 may be compressed andthermally formed through application of heat and pressure to seal thelid 311 to the base 304 and seal around the void 331 and fuse member328.

In the depicted embodiment, the fuse member 328 may be burnt/blown sothat the analyte sensor 300 includes an easy mechanism to determinewhether the analyte sensor 300 has been previously used. For example,functionality within a fuse member burning circuit 410 may burn the fusemember 328 as part of the testing sequence for each analyte sensor 300.Optionally, functionality within the temperature measurement circuit 204or analyte measurement circuit 208 may carry out the burning of the fusemember 328.

Additionally, as part of the analyte testing sequence, functionalitywithin the temperature measurement circuit 204, analyte measurementcircuit 208, or fuse member burning circuit 410 as shown in FIGS. 4-5may, before carrying out an analyte testing sequence, first carry out acheck for a presence of a burnt fuse member 328. If detected, thefunctionality may reject the analyte sensor 300, issue a warning, orotherwise disallow any further testing on the analyte sensor 300.Detection of a burnt fuse member 328 may usually be indicative that theanalyte sensor 300 may have been previously used.

To achieve a burn value (Vb) for the fuse member 328 of about 250 mV orless, the fuse region of reduced area of the fuse member 328 should bemade to be relatively very small. For example, the cross-sectional areamay be about 1.0×10⁻⁵ cm² or less if a gold material is used tomanufacture the fuse member 328. For a carbon-based material, thecross-sectional area may be about 3.7×10⁻⁵ cm² or less. Thus, for a 10mil wide carbon-based burn member, the thickness should be less thanabout 15 μm.

The precise dimensions of the fuse member 328 may be controlled byproducing the fuse region to an oversized dimension in a first step, andthen laser ablating some of the material away via the application of asuitable laser (e.g., an excimer, YAG, or CO₂ laser). In this way, asbest shown in FIGS. 3C-3E, the dimensions of the fuse regions 328A,328B, 328C of the fuse member 328 may be precisely formed andcontrolled, wherein the dotted lines represent the location of theoversized fuse region and the solid lines are the resultantconfiguration after the laser ablation has taken place.

Now referring to the analyte testing system 400 of FIGS. 4-5, the fusemember burning circuit 410 of the analyte testing meter 402 will bedescribed in detail. The fuse member 328 of the analyte sensor 300 willbe burned after the temperature measurements are obtained by thetemperature measurement circuit 204 and sensor 225 and before theanalyte measurement on the analyte sensor 300 is obtained by analytemeasurement circuit 208. To undertake the burn sequence, a signal to theswitch 209 from the processor 205 connects the fuse member burningcircuit 410 to the analyte sensor 300. A signal in line 412 then rampsup the voltage (V_(DAC)) to the amplifier 414 to an appropriate levelwhere the fuse member 328 is burned thereby creating an electrical openacross the fuse member 328. This voltage is designed to be less than thevoltage bias applied across the analyte sensor 300 during the nextanalyte measurement step of the sequence carried out by the analytemeasurement circuit 208. Typically, the applied voltage bias will beabout 300 mV during the analyte measurement phase of the sequence.Therefore, the voltage for the burn of fuse member 328 should be lessthan that; preferably less than about 250 mV, for example. Other lowervoltages may be used, depending upon the burn value of the fuse member328.

Vout may be monitored to determine the occurrence of the burn of thefuse member 328. For example, a slope checking algorithm may be used totest Vout for variations in slope of the Vout signal that are above athreshold value. Such slope excursions are indicative of fuse burning.

Once the burning of the fuse member 328 is accomplished, the switch 209is again activated and the analyte measurement is undertaken by analytemeasurement circuit 208. As is discussed below, the previously obtainedtemperature compensation constant (C_(T)) is used to adjust the rawmeasured analyte value (RMAV) to compensate for temperature at or nearthe location of the reagent on the analyte sensor 300.

FIG. 6 illustrates a variant of the embodiment of FIG. 3A-3B wherein thefuse member 628 of the analyte sensor 600 is provided as a carbon-basedtrace extending between the electrodes 608 and 614. All other featuresare the same as in the FIG. 3A-3B embodiment. In this way, thedimensions and the burn value of the fuse member 628 may be carefullycontrolled by ink-jet printing of the carbon-based trace by applicationof a suitable fusible carbon-based ink.

The first electrode 608 and contact engagement portions 610, 616 may bemanufactured from a second material, e.g., a noble metal thin film. Thethin film may be a gold or platinum film, for example having a thicknessof about 100 nm or less. All other features are the same as in the FIG.3A-3B embodiment. In this way, the analyte sensor 600 may be readilyprepared through the use of a deposition process to deposit the noblemetal portions of the first electrode 608, sensing portion 618, and thecontact engagement portions 610, 616 followed by providing thecarbon-based trace forming the thermocouple portion 626 and the fusemember 628 by an ink-jet process. Additionally, the burn value (Vb) ofthe fuse member 628 may be carefully controlled via the ink jetdeposition process.

FIG. 7 illustrates yet another variant of the embodiment of an analytesensor 700 wherein the sensing portion 718 and the thermocouple portion726 are each formed of a trace of carbon-based material. Optionally, asshown in FIG. 8, a fuse member 828 may be provided as a carbon-basedtrace extending between the electrodes 808 and 814 of the analyte sensor800. In the depicted embodiment of FIG. 7, the first electrode 708 andcontact engagement portions 710, 716 may be manufactured from a firstmaterial, e.g., a noble metal thin film. The thin film may be a gold orplatinum film, having a thickness of about 100 nm or less, for example.All other features are the same as in the FIG. 1A-1B embodiment. In thisway, the sensor 700 may be readily prepared through the use of a firstdeposition process to deposit the noble metal portions of the firstelectrode 708 and the contact engagement portions 710, 716 followed byproviding the carbon-based trace forming the thermocouple portion 726and the sensing portion 718 of the second electrode 714. The secondelectrode 714 and thermocouple portion may be formed via a suitabledeposition process, such as by an ink-jet process depositingcarbon-based ink. Active region 720 may be deposited thereafter.

As discussed above, FIG. 8 illustrates another embodiment of the analytesensor 800. The sensor 800 includes a fuse member 828, thermocoupleportion 826, and sensing portion 818, all being integrally formed from acarbon-based material. In this way, the sensor 800 may be readilyprepared through the use of a first deposition process to deposit thenoble metal portions of the first electrode 808 and the contactengagement portions 810, 816 followed by providing the carbon-basedtrace forming the thermocouple portion 826 and the sensing portion 818of the second electrode 814. The second electrode 814 and thermocoupleportion 826 may be integrally formed via a suitable deposition process,such as by an ink-jet process depositing carbon-based ink. Active region820 may be deposited thereafter.

Methods of testing embodiments of the analyte sensor 300, 600, 800including a thermocouple portion 326, 626, 826 and a fuse member 328,628, 828 according to an aspect of the invention will now be describedwith reference to FIG. 9. In one aspect, the method 900 includes thesteps of providing an analyte sensor in 902, and coupling the analytesensor to an analyte testing meter in 904 (e.g., via insertion in themeter 402 such that the contact engagement portions (e.g., 310, 316) ofthe analyte sensor (e.g., 300) make electrical contact with electricalcontacts (e.g., 206A, 206B) in the analyte test meter (e.g., 402).Ambient temperature is measured by the use of a temperature sensor 225(e.g., a thermistor) positioned at a location in analyte testing meter202 adjacent to the electrical contacts 206A, 206B. The temperaturesensor 225 is used to measure the temperature at a point inside of theanalyte testing meter 202 adjacent to the hot junction. The actualtemperature is the temperature as measured at the temperature sensor 225plus (or minus) the temperature measured on the body of the analytesensor 300 in 908 via the temperature measurement circuit 204. Inparticular, a ΔT is measured between the cold junction and the hotjunction of the thermocouple portion 326. The difference between thecold and hot junction is added (or subtracted as the case may be) fromthe absolute temperature measurement obtained by the sensor 225 at oradjacent to the electrical contacts 206A, 206B. Accordingly, the actualtemperature of the analyte sensor 300 at the cold junction may bedetermined. This temperature, because it is very close to the activeregion 320, may be used to provide a suitable temperature compensationconstant (C_(T)) for the analyte sensor 300. Circuit resistors andcapacitors of the temperature measurement circuit are chosen to providean appropriate temperature compensation constant C_(T) based uponexperimental testing.

Once the temperature of the analyte sensor 300 has been determined, aburning the fuse member 328 on the analyte sensor 300 may beaccomplished in 910. The fuse member burning may be by the operation ofa fuse member burning circuit (e.g., fuse member burning circuit 410shown in FIGS. 4 and 5), for example. Finally, a measured analyte valueis measured on the analyte testing meter in 914 via a conventionalanalyte measurement circuit 208. The calculation of the measured analytevalue is achieved by entirely conventional calculation method and shallnot be described further herein. The only variation is that anadjustment is made in the calculation for both temperature at the coldjunction (using C_(T)) and for lot-to-lot or batch-to-batch calibration(Using C_(C)) as follows:Measured Analyte Value=RMAV×C _(C) ×C _(T)  Equation 1wherein

RMAV=Raw Measured Analyte Value,

C_(C)=Calibration Constant, and

C_(T)=Temperature compensation Constant.

The temperature compensation constant C_(T) may be a linear factor,non-linear factor, or extracted from a lookup table based upon theoutput of the temperature measurement circuit 204, for example.

The method 900 may optionally include a step of checking to see if thefuse member (e.g., fuse member 328) of the analyte sensor (e.g., analytesensor 300) is initially burned in 906 by testing, for example, aresistance across contact engagement portions 310, 316 of the analytesensor 300 directly after coupling the analyte sensor 300 to an analytetesting meter 402 in 904. Once the fuse member 328 is actually burned in910, the method 900 may optionally include a step of checking the fusemember burn in 912 wherein it is checked to see if the fuse member 328of the analyte sensor 300 was properly burned. Again, the test for burnmay be by testing a resistance across contact engagement portions 310,316 of the analyte sensor 300. If resistance is not present, then it isdetermined that the fuse member 328 may be defective or a counterfeit,etc. and the analyte sensor 300 is determined to be not useable. In thiscondition, an error message may be provided to the user. Of course, ifthe fuse member 328 does not burn, then the analyte measurement in 1014cannot be undertaken.

Methods for manufacturing embodiments of the analyte sensors 100, 300 ofthe invention will now be described with reference to FIG. 10. Themethod 1000 includes the steps of providing a base (e.g., a base ofinsulating material) in 1002, and forming a first electrode on a surfaceof the base in 1004. The method 1000 also includes forming a secondelectrode on the base in 1006. The second electrode includes athermocouple portion having a different material composition as comparedto the material composition of the first electrode. In some embodiments,the thermocouple portion may constitute only a portion of the secondelectrode. For example, a first portion of the second electrode mayinclude a sensing portion and a contact engagement portion, and thethermocouple portion may extend there between. The thermocouple portionmay be deposited as a carbon-containing trace. An active region 120 maybe applied to be in contact with at least a portion of the firstelectrode and at least a portion of the second electrode in 1010. Insome embodiments, the active region 120 is provided in contact with onlya small portion of the first and second electrodes. The electrodes maybe formed to include a contact engagement portions adapted to be inelectrical contact with first and second electrical contacts of ananalyte testing meter (see FIGS. 2A-2B and FIGS. 4-5). According to themethod 1000, a lid is applied overtop of the base in 1012 to form acavity in the vicinity of the active region. As discussed above, inorder to form a thermocouple, the first electrode and the thermocoupleportion must be manufactured from different materials.

As discussed above, the electrodes may be made of any suitableelectrically-conductive material, and may be formed by any suitablemethod. For example, one of the electrodes may be formed with aconductive ink (e.g., a carbon-based ink) using a screen printing, laserprinting, or inkjet printing process, for example. Portions of theelectrodes may be integrally formed, or formed as two separatecomponents. In some embodiments, one electrode may be a metal materialsuch as a noble metal (e.g., a gold film). The noble metal may beprovided on the base by a sputtering deposition process. Optionally, theelectrodes may be formed by adhering or forming a thin conductive filmon the base.

The analyte sensors described herein may further include some form ofunderfill detection to determine whether a sufficient amount of thebiological fluid sample is present in the cavity of the analyte sensorin order to carry out an acceptable analyte concentration measurement.For example, underfill detection may be provided by a method describedin United States Application Publication 2009/0095071 to Wu et al.entitled “Underfill Detection System for a Biosensor.” Described is apurely electrical solution wherein the method does not require the useof an additional electrode.

The foregoing description discloses only example embodiments of analytesensors, systems and apparatus including the such analytes sensors, andmethods of manufacturing and using the analyte sensors of the invention.Modifications of the above-disclosed analyte sensors, systems andapparatus incorporating them, and methods for manufacturing and usingthem, which fall within the scope of the invention, will be readilyapparent to those of ordinary skill in the art.

Accordingly, while the present invention has been disclosed inconnection with example embodiments thereof, it should be understoodthat other embodiments may fall within the spirit and scope of theinvention, as defined by the following claims.

The invention claimed is:
 1. An analyte sensor, comprising: a firstelectrode having a contact engagement portion and a sensing portion; asecond electrode having a contact engagement portion and a sensingportion; an active region provided in contact with, and extendingbetween, the sensing portions of the first electrode and the secondelectrode; and a thermocouple portion comprising at least part of aconducting path from the active region to the contact engagement portionof the second electrode.
 2. The analyte sensor of claim 1, wherein thefirst electrode comprises a working electrode, and the second electrodecomprises a counter or reference electrode.
 3. The analyte sensor ofclaim 1, wherein the contact engagement portions are the only twocontact engagement portions of the analyte sensor.
 4. The analyte sensorof claim 1, further comprising a base, the first electrode and thesecond electrode extending along the base.
 5. The analyte sensor ofclaim 1, wherein the first electrode comprises a different conductivematerial than the thermocouple portion of the second electrode.
 6. Theanalyte sensor of claim 1, wherein the thermocouple portion comprises acarbon-based material.
 7. The analyte sensor of claim 4, wherein thefirst electrode comprises a noble metal and the thermocouple portioncomprises a carbon-based material.
 8. The analyte sensor of claim 1,further comprising a fuse member extending between the first electrodeand the second electrode.
 9. The analyte sensor of claim 8, wherein thefuse member is manufactured from the same material as the firstelectrode.
 10. The analyte sensor of claim 8, wherein the fuse memberhas a burn value that is less than 250 mV.
 11. The analyte sensor ofclaim 8, wherein the fuse member has a burn value that is less than aconstant voltage bias adapted to be received across the active regionduring an analyte measurement test.
 12. The analyte sensor of claim 8,wherein the thermocouple portion comprises a carbon trace extending froma reference junction at the contact engagement portion of the secondelectrode and a sensing junction adjacent to the fuse member.